PHASE 2 TRIAL OF AG-013736 AS FIRST-LINE TREATMENT FOR PATIENTS WITH SQUAMOUS NON-SMALL CELL LUNG CANCER RECEIVING TREATMENT WITH CISPLATIN AND GEMCITABINE

• Conditions: Advanced non-small cell lung cancer; MedDRA version: 9.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastatic; MedDRA version: 9.1Level: LLTClassification code 10029515Term: Non-small cell lung cancer recurrent; MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IV

• Registration Number: EUCTR2008-001726-13-PL
• Lead Sponsor: Pfizer Inc, 235 East 42nd Street, New York City, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Histologically- or cytologically-confirmed diagnosis of squamous NSCLC
• Cytologic specimens for diagnosis must have been obtained from bronchial brushings or washings or from needle aspiration of a defined lesion. Sputum cytology alone will not be sufficient for diagnosis.
• Patients with mixed NSCLC histology should be classified by the predominant
histologic type.
2. Stage IIIB with malignant effusion (fluid cytology demonstrating malignant cells
required), Stage IV, or recurrent disease after definitive local therapy
3. Candidate for primary treatment with cisplatin and gemcitabine
4. Presence of measurable disease by RECIST
5. Adequate organ function as defined by the following criteria:
a. Absolute neutrophil count (ANC) =1500 cells/mm3
b. Platelet count =100,000 cells/mm3
c. Hemoglobin =9 g/dL
d. AST and ALT =<2.5 x ULN, or AST and ALT =<5 x ULN if liver function
abnormalities are due to underlying malignancy
e. Total bilirubin =1.5 x ULN
f. Calculated creatinine clearance or measured creatinine clearance =60 mL/min.
g. Urine protein < 1+ by dipstick. If dipstick is = 1+ then urine protein:creatinine ratio
must be < 1 to be eligible.
6. Age =18 years
7. Life expectancy >12 weeks
8. ECOG performance status of 0 or 1
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
10. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior systemic treatment for Stage IIIB (with malignant effusion) or Stage IV NSCLC. Adjuvant chemotherapy or chemoradiation (sequential or concomitant) is permitted if the last dose of systemic therapy was =12 months prior to start of study treatment
2. Prior treatment with a VEGF or VEGFR inhibitor
3. Radiation therapy within 21 days, major surgery within 28 days, or minor procedures including fine needle aspiration within 7 days of study treatment. All acute toxicities must have resolved to baseline or to CTC Grade 1 (NCI CTCAE v3.0).
4. One or more lung lesions with cavitation, or any lesion invading or abutting a major blood vessel as assessed by CT or MRI.
5. History of hemoptysis > ½ tsp (2.5 ml) of blood per day for a day or more within 1 week of study treatment, or Grade 3 or 4 hemoptysis within 4 weeks of study treatment
6. NCI CTCAE Grade 3 hemorrhage from any cause within 4 weeks of study treatment
7. Preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be =140 mm Hg, and the baseline diastolic blood pressure readings must be =90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible
8. Untreated brain metastases. Patients with previously diagnosed CNS metastases are eligible if they have completed radiation therapy to the brain at least 4 weeks prior to study treatment, have recovered from the acute effects of that treatment, have discontinued corticosteroid treatment for at least 2 weeks prior to study treatment, and are eurologically stable
9. Seizure = 28 days or use of an anticonvulsant =14 days prior to study treatment.
10. History of a bleeding diathesis or coagulopathy = 12 months of study entry
11. Need for therapeutic anticoagulation, regular use of aspirin (> 325 mg/day), NSAID or other medications known to inhibit platelet function. (Low-dose anticoagulants, such as low-dose heparin or =2 mg/day of warfarin for prevention of deep venous thrombosis or maintenance of patency of central venous access devices is permitted).
12. Any of the following = 12 months prior to study treatment: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism
13. Gastrointestinal abnormalities including inability to take oral medication, requirement for intravenous alimentation, prior total gastric resection, treatment for endoscopy confirmed active peptic ulcer disease within 6 months prior to study treatment, active gastrointestinal bleeding (as evidenced by hematemesis, hematochezia or melena) within 3 months of study treatment, or malabsorption syndromes
14. Positive serum or urine pregnancy test within 7 days of study treatment. (Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter.)
15. Female patients who are breastfeeding
16.Active malignancies except for NSCLC
17. Neuropathy (Grade = 2 CTCAE Version 3.0) or known high frequency range hearing impairment
18. Known hypersensitivity to gemcitabine or one of its inactive ingredients or to cisplatin or other platinum compounds, or any other known or suspected contraindications to receive treatment with gemcitabine and cis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of AG-013736 in combination with cisplatin/gemcitabine in<br>patients with advanced/metastatic, squamous NSCLC.;Secondary Objective: • To assess the safety of AG-013736 in combination with cisplatin/gemcitabine in<br>patients with squamous NSCLC<br>• To assess population pharmacokinetics for AG-013736<br>• To explore VEGF receptor signaling in circulating endothelial cells in this patient<br>population;Primary end point(s): Overall confirmed objective response rate (ORR), defined as the proportion of<br>patients with a confirmed best response characterized as either a complete<br>response (CR) or partial response (PR) (target lesions and tumor response defined<br>according to RECIST guidelines). Confirmed responses are those that persist on a<br>follow-up imaging assessment =4 weeks after the initial objective documentation<br>of response.